More than 25% of the population suffer from IgE-mediated allergies, which can involve symptoms ranging from milder ones such as hay fever to serious episodes of asthma or anaphylactic shock. These allergies may be due to environmental allergens such as pollens, mites, insects, and the like, or food allergens such as peanuts, shellfish, eggs, milk, wheat, tree nuts, and the like. Exposure to an allergen following allergic sensitization (e.g., the initial exposure to the allergen and subsequent induction of allergen-specific IgE antibodies) leads to cross-linking of the allergen specific-IgE antibodies bound to the surface of mast cells and basophils, degranulation of these cells, and release of inflammatory mediators, proteases, and pro-inflammatory cytokines that lead to the symptoms associated with early or acute allergic reactions.
Pharmaceutical treatment of allergy has focused on mitigation of allergic inflammation and often provides only temporary relief to the individual. Allergen-specific immunotherapy (SIT), on the other hand, is designed to provide long-last effects by modifying the individual's allergen-specific immune response. SIT is based on the repeated administration of a specific allergen to the individual over a period of time, e.g., years, such that the individual becomes desensitized to the allergen and can tolerate higher doses of the allergen without developing an allergic reaction. SIT involves the induction of antibodies against a specific allergen which block, and not enhance an allergic reaction. Traditional allergen-specific immunotherapy involves administration of allergen extracts or recombinant allergens which can cause side effects such as inflammatory response and anaphylactic reactions. In addition, traditional SIT is time consuming and often fails to achieve its goal of desensitizing the individual to the Allergan.
Allergies to shellfish, e.g., shrimp, lobster, oysters, etc., are one of the most common food allergies. The major allergen in shrimp is an invertebrate tropomyosin protein. At least 80% of shrimp-allergic subjects react to tropomyosin and the protein binds approximately 85% of the shrimp-specific IgE from shrimp-allergic subjects. Recent studies have shown that tropomyosin is a cross-reactive allergen and is found in other crustaceans such as lobster, crab, squid, snail and oyster, as well as other invertebrates such as the house dust mite and cockroach (Ayuso et al., Int Arch Allergy Immunol, 2002, 129:38-48). A strong positive correlation has been established between IgE-mediated sensitization to shrimp, cockroach and dust mite (Wang et al., J Allergy Clin Immunol, 2011, 128(4):834-7; Shafique et al., Allergy Rhinol, 2012, 3:e74-e90).
There remains a need in the art for novel and efficacious therapies for allergies to invertebrate tropomyosins. The present invention satisfies this need and provides additional advantages as well.